The long-acting beta2-agonist salmeterol xinafoate: effects on airway inflammation in asthma

Salmeterol xinafoate is an inhaled long-acting beta2-adrenoceptor agonist recently introduced for the treatment of asthma. Both in vitro and animal studies suggest that it may have anti-inflammatory activities of benefit in this disease. To assess this directly, the effects of 6 weeks' treatment with salmeterol on indices of clinical activity, airway dysfunction and inflammation in subjects with stable atopic asthma were investigated. In a double blind study, asthmatic patients were randomized to 6 weeks' treatment with either salmeterol 50 microg twice daily (n=14) or placebo (n=12). They underwent bronchoscopy with bronchoalveolar lavage (BAL) and bronchial biopsy immediately before starting treatment and again after 6 weeks. Treatment with salmeterol improved clinical indices of asthma activity, but there were no changes in BAL differential cell counts or mediator levels, and no change in T-cell numbers or activation status. In the biopsy specimens there were no changes in numbers of inflammatory cells, sub-basement membrane collagen deposition or mast cell degranulation. Regular treatment with salmeterol improves clinical indices of asthma but has no effect on the underlying inflammatory process. These findings strengthen guideline recommendations that long-acting beta2-agonists should not be prescribed as sole antiasthma medication.

This article has been cited by other articles:

				A. Sindi, D. C. Todd, and P. Nair Antiinflammatory Effects of Long-Acting {beta}2-Agonists in Patients With Asthma: A Systematic Review and Metaanalysis Chest, July 1, 2009; 136(1): 145 - 154. [Abstract] [Full Text] [PDF]

				M. Kaur, N. S. Holden, S. M. Wilson, M. B. Sukkar, K. F. Chung, P. J. Barnes, R. Newton, and M. A. Giembycz Effect of {beta}2-adrenoceptor agonists and other cAMP-elevating agents on inflammatory gene expression in human ASM cells: a role for protein kinase A Am J Physiol Lung Cell Mol Physiol, September 1, 2008; 295(3): L505 - L514. [Abstract] [Full Text] [PDF]

				M. Kaur, J. E. Chivers, M. A. Giembycz, and R. Newton Long-Acting 2-Adrenoceptor Agonists Synergistically Enhance Glucocorticoid-Dependent Transcription in Human Airway Epithelial and Smooth Muscle Cells Mol. Pharmacol., January 1, 2008; 73(1): 203 - 214. [Abstract] [Full Text] [PDF]

				R. H. Green, C. E. Brightling, S. McKenna, B. Hargadon, N. Neale, D. Parker, C. Ruse, I. P. Hall, and I. D. Pavord Comparison of asthma treatment given in addition to inhaled corticosteroids on airway inflammation and responsiveness Eur. Respir. J., June 1, 2006; 27(6): 1144 - 1151. [Abstract] [Full Text] [PDF]

				K. Maneechotesuwan, S. Essilfie-Quaye, S. Meah, C. Kelly, S. A. Kharitonov, I. M. Adcock, and P. J. Barnes Formoterol Attenuates Neutrophilic Airway Inflammation in Asthma Chest, October 1, 2005; 128(4): 1936 - 1942. [Abstract] [Full Text] [PDF]

				G.P. Currie, P. Srivastava, O.J. Dempsey, and D.K.C. Lee Therapeutic modulation of allergic airways disease with leukotriene receptor antagonists QJM, March 1, 2005; 98(3): 171 - 182. [Abstract] [Full Text] [PDF]

				S. R. Salpeter, T. M. Ormiston, and E. E. Salpeter Meta-Analysis: Respiratory Tolerance to Regular {beta}2-Agonist Use in Patients with Asthma Ann Intern Med, May 18, 2004; 140(10): 802 - 813. [Abstract] [Full Text] [PDF]

				G.P. Currie, C.M. Jackson, S.A. Ogston, and B.J. Lipworth Airway-stabilizing effect of long-acting {beta}2-agonists as add-on therapy to inhaled corticosteroids QJM, June 1, 2003; 96(6): 435 - 440. [Abstract] [Full Text] [PDF]

				G. P. Currie, D. K. C. Lee, K. Haggart, C. E. Bates, and B. J. Lipworth Effects of Montelukast on Surrogate Inflammatory Markers in Corticosteroid-treated Patients with Asthma Am. J. Respir. Crit. Care Med., May 1, 2003; 167(9): 1232 - 1238. [Abstract] [Full Text] [PDF]

				M J Vaquerizo, P Casan, J Castillo, M Perpina, J Sanchis, V Sobradillo, A Valencia, H Verea, J L Viejo, C Villasante, et al. Effect of montelukast added to inhaled budesonide on control of mild to moderate asthma Thorax, March 1, 2003; 58(3): 204 - 210. [Abstract] [Full Text] [PDF]

				P A Beckett and P H Howarth Pharmacotherapy and airway remodelling in asthma? Thorax, February 1, 2003; 58(2): 163 - 174. [Abstract] [Full Text] [PDF]

				P.K. Jeffery, P. Venge, M.J. Gizycki, I. Egerod, R. Dahl, and P. Faurschou Effects of salmeterol on mucosal inflammation in asthma: a placebo-controlled study Eur. Respir. J., December 1, 2002; 20(6): 1378 - 1385. [Abstract] [Full Text] [PDF]

				N. J. Vanacker, E. Palmans, R. A. Pauwels, and J. C. Kips Effect of Combining Salmeterol and Fluticasone on the Progression of Airway Remodeling Am. J. Respir. Crit. Care Med., October 15, 2002; 166(8): 1128 - 1134. [Abstract] [Full Text] [PDF]

				B. J. Lipworth and C. M. Jackson Bronchodilator Reversibility to Albuterol Predicts Bronchodilator Response to Salmeterol Chest, April 1, 2002; 121(4): 1382 - 1382. [Full Text] [PDF]

				P.J. Barnes Scientific rationale for inhaled combination therapy with long-acting {beta}2-agonists and corticosteroids Eur. Respir. J., January 1, 2002; 19(1): 182 - 191. [Abstract] [Full Text] [PDF]

				J. C. KIPS and R. A. PAUWELS Long-acting Inhaled beta 2-Agonist Therapy in Asthma Am. J. Respir. Crit. Care Med., September 15, 2001; 164(6): 923 - 932. [Full Text] [PDF]

				S. J. WILSON, A. WALLIN, G. DELLA-CIOPPA, T. SANDSTROM, and S. T. HOLGATE Effects of Budesonide and Formoterol on NF-kappa B, Adhesion Molecules, and Cytokines in Asthma Am. J. Respir. Crit. Care Med., September 15, 2001; 164(6): 1047 - 1052. [Abstract] [Full Text] [PDF]

				A.J. Knox, Y.M. Zhu, and L. Pang Do long-acting {beta}2-adrenoceptor agonists enhance the anti-inflammatory effect of glucocorticoids in asthma? Eur. Respir. J., June 1, 2001; 17(6): 1059 - 1061. [Full Text] [PDF]

				R. F. Lemanske Jr, C. A. Sorkness, E. A. Mauger, S. C. Lazarus, H. A. Boushey, J. V. Fahy, J. M. Drazen, V. M. Chinchilli, T. Craig, J. E. Fish, et al. Inhaled Corticosteroid Reduction and Elimination in Patients With Persistent Asthma Receiving Salmeterol: A Randomized Controlled Trial JAMA, May 23, 2001; 285(20): 2594 - 2603. [Abstract] [Full Text] [PDF]

				S. T. Holgate Therapeutic Options for Persistent Asthma JAMA, May 23, 2001; 285(20): 2637 - 2639. [Full Text] [PDF]

				W. J. CALHOUN, K. L. HINTON, and J. J. KRATZENBERG The Effect of Salmeterol on Markers of Airway Inflammation Following Segmental Allergen Challenge Am. J. Respir. Crit. Care Med., March 15, 2001; 163(4): 881 - 886. [Abstract] [Full Text]

				I. Aziz, A. M. Wilson, and B. J. Lipworth Effects of Once-Daily Formoterol and Budesonide Given Alone or in Combination on Surrogate Inflammatory Markers in Asthmatic Adults Chest, October 1, 2000; 118(4): 1049 - 1058. [Abstract] [Full Text] [PDF]